RO4929097

RO4929097
Identifiers
	IUPAC name 2,2-Dimethyl-N-[(10S)-9-oxo-8-azatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-10-yl]-'N′-(2,2,3,3,3-pentafluoropropyl)propanediamide;
CAS Number	847925-91-1;
PubChem CID	49867930;
ChemSpider	25027400;
UNII	KK8645V7LE;
CompTox Dashboard (EPA)	DTXSID20233833 ;
Chemical and physical data
Formula	C22H20F5N3O3
Molar mass	469.412 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C1Nc2ccccc2c2c(C1NC(=O)C(C(=O)NCC(C(F)(F)F)(F)F)(C)C)cccc2;
	InChI InChI=1S/C22H20F5N3O3/c1-20(2,18(32)28-11-21(23,24)22(25,26)27)19(33)30-16-14-9-4-3-7-12(14)13-8-5-6-10-15(13)29-17(16)31/h3-10,16H,11H2,1-2H3,(H,28,32)(H,29,31)(H,30,33)/t16-/m0/s1; Key:OJPLJFIFUQPSJR-INIZCTEOSA-N;

RO4929097 (RG-4733) is a gamma secretase inhibitor being studied as an anti-cancer drug.^[1] Targeting gamma secretase inhibits NOTCH signaling, which is upregulated in many forms of cancer.^[2] The drug was initially developed by Roche for the treatment of Alzheimer's disease, but current research focuses on cancer.^[3] Production was halted in 2010, but began again in 2014.^[4]

Research

Over 35 phase I and II clinical trials have been performed, but no phase III trials have yet commenced.^[5] Phase II studies have investigated the use of RO4929097 in ovarian cancer,^[6] renal cell carcinoma in patients that were unsuccessful on anti-VEGF treatments,^[7] metastatic pancreatic cancer,^[8] advanced brain tumors,^[9] and relapsed non-small cell lung cancer.^[10]

Other planned clinical trials were terminated, because the drug became unavailable.^[11]

References

^ Luistro L, He W, Smith M, Packman K, Vilenchik M, Carvajal D, Roberts J, Cai J, Berkofsky-Fessler W, Hilton H, Linn M, Flohr A, Jakob-Røtne R, Jacobsen H, Glenn K, Heimbrook D, Boylan JF (October 2009). "Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties". Cancer Research. 69 (19): 7672–80. doi:10.1158/0008-5472.CAN-09-1843. PMC 5260798. PMID 19773430.
^ "Gamma-secretase/Notch signalling pathway inhibitor RO4929097". NCI Drug Dictionary. National Cancer Institute.
^ "RO4929097". IUPHAR/BPS Guide to PHARMACOLOGY.
^ "RG 4733". AdisInsight. Springer Nature Switzerland AG.
^ "Search for: RO4929097 - List Results - ClinicalTrials.gov".
^ Clinical trial number NCT01175343 for "RO4929097 in Treating Patients With Recurrent and/or Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer" at ClinicalTrials.gov
^ Clinical trial number NCT01141569 for "A Study of RO4929097 in Patients With Advanced Renal Cell Carcinoma That Have Failed Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR) Therapy" at ClinicalTrials.gov
^ Clinical trial number NCT01232829 for "Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer" at ClinicalTrials.gov
^ Clinical trial number NCT01122901 for "Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Recurrent or Progressive Glioblastoma" at ClinicalTrials.gov
^ Clinical trial number NCT01070927 for "An Exploratory Study of RO4929097 in Patients With Recurrent or Refractory Non-Small Cell Lung Cancer" at ClinicalTrials.gov
^ Clinical trial number NCT01216787 for "RO4929097 in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Melanoma That Can Be Removed by Surgery" at ClinicalTrials.gov

[pmid19773430-1] Luistro L, He W, Smith M, Packman K, Vilenchik M, Carvajal D, Roberts J, Cai J, Berkofsky-Fessler W, Hilton H, Linn M, Flohr A, Jakob-Røtne R, Jacobsen H, Glenn K, Heimbrook D, Boylan JF (October 2009). "Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties". Cancer Research. 69 (19): 7672–80. doi:10.1158/0008-5472.CAN-09-1843. PMC 5260798. PMID 19773430.

[2] "Gamma-secretase/Notch signalling pathway inhibitor RO4929097". NCI Drug Dictionary. National Cancer Institute.

[3] "RO4929097". IUPHAR/BPS Guide to PHARMACOLOGY.

[4] "RG 4733". AdisInsight. Springer Nature Switzerland AG.

[5] "Search for: RO4929097 - List Results - ClinicalTrials.gov".

[6] Clinical trial number NCT01175343 for "RO4929097 in Treating Patients With Recurrent and/or Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer" at ClinicalTrials.gov

[7] Clinical trial number NCT01141569 for "A Study of RO4929097 in Patients With Advanced Renal Cell Carcinoma That Have Failed Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR) Therapy" at ClinicalTrials.gov

[8] Clinical trial number NCT01232829 for "Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer" at ClinicalTrials.gov

[9] Clinical trial number NCT01122901 for "Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Recurrent or Progressive Glioblastoma" at ClinicalTrials.gov

[10] Clinical trial number NCT01070927 for "An Exploratory Study of RO4929097 in Patients With Recurrent or Refractory Non-Small Cell Lung Cancer" at ClinicalTrials.gov

[11] Clinical trial number NCT01216787 for "RO4929097 in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Melanoma That Can Be Removed by Surgery" at ClinicalTrials.gov

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